Region-specific tauopathy and synucleinopathy in brain of the alpha-synuclein overexpressing mouse model of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>α-synuclein [α-Syn]-mediated activation of GSK-3β leading to increases in hyperphosphorylated Tau has been shown by us to occur in striata of Parkinson's diseased [PD] patients and in animal models of PD. In Alzheimer's disease, tauopathy exists in several brain regions; however, the pattern of distribution of tauopathy in other brain regions of PD or in animal models of PD is not known. The current studies were undertaken to analyze the distribution of tauopathy in different brain regions in a widely used mouse model of PD, the α-Syn overexpressing mouse.</p> <p>Results</p> <p>High levels of α-Syn levels were seen in the brain stem, with a much smaller increase in the frontal cortex; neither cerebellum nor hippocampus showed any overexpression of α-Syn. Elevated levels of p-Tau, hyperphosphorylated at Ser202, Ser262 and Ser396/404, were seen in brain stem, with lower levels seen in hippocampus. In both frontal cortex and cerebellum, increases were seen only in p-Ser396/404 Tau, but not in p-Ser202 and p-Ser262. p-GSK-3β levels were not elevated in any of the brain regions, although total GSK-3β was elevated in brain stem. p-p38MAPK levels were unchanged in all brain regions examined, while p-ERK levels were elevated in brain stem, hippocampus and cerebellum, but not the frontal cortex. p-JNK levels were increased in brain stem and cerebellum but not in the frontal cortex or hippocampus. Elevated levels of free tubulin, indicating microtubule destabilization, were seen only in the brain stem.</p> <p>Conclusion</p> <p>Our combined data suggest that in this animal model of PD, tauopathy, along with microtubule destabilization, exists primarily in the brain stem and striatum, which are also the two major brain regions known to express high levels of α-Syn and undergo the highest levels of degeneration in human PD. Thus, tauopathy in PD may have a very restricted pattern of distribution.</p

Child and Parent Report of Parenting as Predictors of Substance Use and Suspensions from School

This study examined how child and parent reports of parenting were related to early adolescent substance use and school suspensions. Data were from two time points six months apart on 321 families with an eighth grade student attending one of five schools in the Pacific Northwest. Child- and parent-report measures of family management practices were moderately correlated (r = .29). Child report, but not parent report, of more positive family management practices uniquely predicted a lower likelihood of adolescent substance use. Also, discrepancies between child and parent report of parenting predicted substance use, with child positive report of family management losing its protective association with adolescent substance use when parents had negative reports of their parenting. Parent report, but not child report, of better parenting predicted lower likelihood of suspensions, suggesting that the salience of child and parent report may depend on the type of behavioral outcome

Child and Parent Report of Parenting as Predictors of Substance Use and Suspensions from School

This study examined how child and parent reports of parenting were related to early adolescent substance use and school suspensions. Data were from two time points six months apart on 321 families with an eighth grade student attending one of five schools in the Pacific Northwest. Child- and parent-report measures of family management practices were moderately correlated (r = .29). Child report, but not parent report, of more positive family management practices uniquely predicted a lower likelihood of adolescent substance use. Also, discrepancies between child and parent report of parenting predicted substance use, with child positive report of family management losing its protective association with adolescent substance use when parents had negative reports of their parenting. Parent report, but not child report, of better parenting predicted lower likelihood of suspensions, suggesting that the salience of child and parent report may depend on the type of behavioral outcome

A new approach to generating research-quality data through citizen science: The USA National Phenology Monitoring System

Phenology is one of the most sensitive biological responses to climate change, and recent changes in phenology have the potential to shake up ecosystems. In some cases, it appears they already are. Thus, for ecological reasons it is critical that we improve our understanding of species&#x2019; phenologies and how these phenologies are responding to recent, rapid climate change. Phenological events like flowering and bird migrations are easy to observe, culturally important, and, at a fundamental level, naturally inspire human curiosity&#x2014; thus providing an excellent opportunity to engage citizen scientists. The USA National Phenology Network has recently initiated a national effort to encourage people at different levels of expertise&#x2014;from backyard naturalists to professional scientists&#x2014;to observe phenological events and contribute to a national database that will be used to greatly improve our understanding of spatio-temporal variation in phenology and associated phenological responses to climate change.&#xd;&#xa;&#xd;&#xa;Traditional phenological observation protocols identify specific dates at which individual phenological events are observed. The scientific usefulness of long-term phenological observations could be improved with a more carefully structured protocol. At the USA-NPN we have developed a new approach that directs observers to record each day that they observe an individual plant, and to assess and report the state of specific life stages (or phenophases) as occurring or not occurring on that plant for each observation date. Evaluation is phrased in terms of simple, easy-to-understand, questions (e.g. &#x201c;Do you see open flowers?&#x201d;), which makes it very appropriate for a citizen science audience. From this method, a rich dataset of phenological metrics can be extracted, including the duration of a phenophase (e.g. open flowers), the beginning and end points of a phenophase (e.g. traditional phenological events such as first flower and last flower), multiple distinct occurrences of phenophases within a single growing season (e.g multiple flowering events, common in drought-prone regions), as well as quantification of sampling frequency and observational uncertainties. These features greatly enhance the utility of the resulting data for statistical analyses addressing questions such as how phenological events vary in time and space, and in response to global change. This new protocol is an important step forward, and its widespread adoption will increase the scientific value of data collected by citizen scientists.&#xd;&#xa

Gastroenteritis and Transmission of Helicobacter pylori Infection in Households1

In northern California homes, exposure to gastroenteritis in an H. pylori–infected contact markedly increased H. pylori infection

Synthetic Compound Libraries Displayed on the Surface of Encoded Bacteriophage

AbstractWe describe a technology for attaching libraries of synthetic compounds to coat proteins of bacteriophage particles such that the identity of the chemical structure is encoded in the genome of the phage, analogous to peptides displayed on phage surfaces by conventional phage-display techniques. This format allows a library of synthetic compounds to be screened very efficiently as a single pool. Encoded phage serve as extremely robust reporters of the presence of each compound, providing exquisite sensitivity for identification of active compounds engaged in complex biological processes such as receptor-mediated endocytosis and transcytosis. To evaluate this approach, we constructed a library of 980 analogs of folic acid displayed on T7 phage, and demonstrated rapid identification of compounds that bind to folate receptor and direct endocytosis of associated phage particles into cells that express the targeted receptor

The complete genome of klassevirus – a novel picornavirus in pediatric stool

<p>Abstract</p> <p>Background</p> <p>Diarrhea kills 2 million children worldwide each year, yet an etiological agent is not found in approximately 30–50% of cases. Picornaviral genera such as enterovirus, kobuvirus, cosavirus, parechovirus, hepatovirus, teschovirus, and cardiovirus have all been found in human and animal diarrhea. Modern technologies, especially deep sequencing, allow rapid, high-throughput screening of clinical samples such as stool for new infectious agents associated with human disease.</p> <p>Results</p> <p>A pool of 141 pediatric gastroenteritis samples that were previously found to be negative for known diarrheal viruses was subjected to pyrosequencing. From a total of 937,935 sequence reads, a collection of 849 reads distantly related to Aichi virus were assembled and found to comprise 75% of a novel picornavirus genome. The complete genome was subsequently cloned and found to share 52.3% nucleotide pairwise identity and 38.9% amino acid identity to Aichi virus. The low level of sequence identity suggests a novel picornavirus genus which we have designated klassevirus. Blinded screening of 751 stool specimens from both symptomatic and asymptomatic individuals revealed a second positive case of klassevirus infection, which was subsequently found to be from the index case's 11-month old twin.</p> <p>Conclusion</p> <p>We report the discovery of human klassevirus 1, a member of a novel picornavirus genus, in stool from two infants from Northern California. Further characterization and epidemiological studies will be required to establish whether klasseviruses are significant causes of human infection.</p

Impacts of water level on metabolism and transient storage in vegetated lowland rivers: insights from a mesocosm study

Transient storage zones for water represent potential hot spots for metabolic activity in streams. In lowland rivers, the high abundance of submerged vegetation can increase water transient storage, bioreactive surface areas and, ultimately, in-stream metabolic activity. Changes in flow resulting from climatic and anthropogenic factors that influence the presence of aquatic vegetation can also, thereby, impact in-stream metabolism and nutrient cycling. We investigated the effects of water column depth on aquatic vegetation cover and its implications on water transient storage and associated metabolic activity in stream mesocosms (n=8) that represent typical conditions of lowland streams. Continuous injections of metabolically reactive (resazurin-resorufin) tracers were conducted and used to quantify hydraulic transport and whole-mesocosm aerobic respiration. Acetate, a labile carbon source, was added during a second stage of the tracer injection to investigate metabolic responses. We observed both higher vegetation coverage and resazurin uptake velocity, used as a proxy of mesocosm respiration, with increasing water column depth. The acetate injection had a slight, positive effect on metabolic activity. A hydrodynamic model estimated the water transport and retention characteristics and first-order reactivity for three mesocosms. These results suggest that both the vegetated surface water and sediments contribute to metabolically active transient storage within the mesocosms, with vegetation having a greater influence on ecosystem respiration. Our findings suggest that climate and external factors that affect flow and submerged vegetation of lowland rivers will result in changes in stream respiration dynamics and that submerged vegetation are a particularly important and sensitive location for stream respiration

What do measures of patient satisfaction with the doctor tell us?

Objective: To gain an understanding of how patient satisfaction (PS) with the doctor (PSD) is conceptualized through an empirical review of how it is currently being measured. The content of PS questionnaire items was examined to (a) determine the primary domains underlying PSD, and (b) summarize the specific doctor-related characteristics and behaviors, and patient-related perceptions, composing each domain. Methods: A scoping review of empirical articles that assessed PSD published from 2000 to November 2013. MEDLINE and PsycINFO databases were searched. Results: The literature search yielded 1726 articles, 316 of which fulfilled study inclusion criteria. PSD was realized in one of four health contexts, with questions being embedded in a larger questionnaire that assessed PS with either: (1) overall healthcare, (2) a specific medical encounter, or (3) the healthcare team. In the fourth context, PSD was the questionnaire's sole focus. Five broad domains underlying PSD were revealed: (1) Communication Attributes; (2) Relational Conduct; (3) Technical Skill/Knowledge; (4) Personal Qualities; and (5) Availability/Accessibility. Conclusions: Careful consideration of measurement goals and purposes is necessary when selecting a PSD measure. Practice implications: The five emergent domains underlying PSD point to potential key areas of physician training and foci for quality assessment